A variety of synthetic porphyrins designed to mimic oxygen carriers have been proposed. Some examples include "capped" porphyrins (Almog, 1975, 1981; Baldwin), "bridged" porphyrins (Battersby, 1976, 1978); "picket fence" porphyrins (Collman, 1973, 1975), "pocket" porphyrins (Collman, 1981, 1983), "basket-handle" porphyrins (Momenteau, 1979, 1980, 1983), "gyroscope" porphyrins (Lecas, Boitrel), "cyclophane" porphyrins (Diekman, Traylor), and "jelly-fish" type porphyrins (Uemori).
In general, structures such as noted above include a porphyrin ring which is bound to a transition metal such as iron or cobalt, and an axial ligand which protects one of the axial coordination sites of the metal from irreversible oxidation processes. In some structures, the ligand is covalently attached to the porphyrin ring. However, such covalent attachment requires multistep synthetic reaction schemes that are lengthy or produce the desired compound in low overall yield. More typically, the axial ligand is not covalently attached to the porphyrin. In such cases, where the porphyrin compound is used in a liquid, the ligand is included in the liquid, usually in a 100- to 1000-fold excess relative to the porphyrin compound, to ensure saturation of the axial coordination site of the metal. In other cases, where the porphyrin compound is contained in a dry solid phase, the ligand can be provided by the solid phase itself, thereby linking the porphyrin compound to the solid phase.
It is well known that the affinities of axial ligands for porphyrin metals vary according to the nature of the particular ligand. The ligand is usually selected not only to protect the metal from oxidation, but also to modulate the relative affinity of the porphyrin metal for a selected small molecule such as oxygen or carbon monoxide. Nitrogen-containing ligands such as imidazoles and pyridines are known to bind relatively strongly to porphyrin metals (e.g., iron and cobalt), whereas other ligands, such as thiolates, typically bind weakly, and are needed in high concentrations (for liquid applications) to attain high axial site occupancy. Moreover, since the binding of ligands to porphyrin metals is reversible, the porphyrin is constantly, albeit transiently, susceptible to irreversible oxidation during the time that ligand is not bound to the axial site. It would therefore be desirable to provide a porphyrin complex in which the affinity for the axial ligand is enhanced, but without invoking covalent attachment of the ligand to the porphyrin.
In addition, there has been interest in the development of water-soluble oxygen carriers. U.S. Pat. Nos. 4,602,987, 4,609,383, and 4,629,544 disclose the use of water-soluble, porphyrin-containing proteins such as hemoglobin for extracting oxygen from fluids. Subsequent to the issue of those patents, however, it has been reported that the large molecular weight of hemoglobin, its limited water solubility, and the high overpotentials needed in redox reactions with hemoglobin place serious limitations on such use (De Castro, 1990).
Ideally, a water-soluble oxygen carrier or binding compound should be easy to synthesize, have a high oxygen-binding affinity and yet be amenable to deoxygenation under selected conditions, be resistant to oxidative degradation, and be able to withstand heating without isomerization.